#324

Yes I have reached longevity escape velocity for worms. Xprize, the money is mine…

5 Likes
#325

Great. They answered almost immediately, and they say that the results in my both experiments are all good. They terminated the worms that are still alive in the experiment after 30 days. So I think I can celebrate a life extension success with my two experiments. I have a few ideas.

"Hi !

The data is QC’d and accurate :blush: Both of those treatments had very impressive lifespan extension results!

As a little context, we typically only run experiments for 30 days. In both of those experiments, by the time we ended the experiment (Day 31 for Order 9191 and Day 36 for Order 9168), there were still a large proportion of animals still alive! For 9191, we were unable to resolve a median lifespan by the time we ended the assay due to this impressive lifespan extension!

Doxycycline is a known lifespan extending intervention in C. elegans. In our system, antibiotics typically extend because we use live (as opposed to killed) bacteria as a food source. It is very interesting to think about whether an mTOR inhibitor like GSK2126458 would extend in the context of doxycycline. To better understand that we would need to run each compound separately in addition to the combination. Would also be interesting to evaluate the combination in the context of killed food. Let us know if you are interested in any further tests and I’ll send over a custom study quote.

Best wishes and thank you again for contributing to the Million Molecule Challenge!

Dr. Mitchell Lee (He/Him)
CEO & Co-Founder
Ora Biomedical, Inc."

Ora Results.pdf (501.2 KB)
Ora Results 2.pdf (261.9 KB)

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#326

Really impressive indeed!
They mention that " Doxycycline is a known lifespan extending intervention in C. elegans. In our system, antibiotics typically extend because we use live (as opposed to killed) bacteria as a food source."
Do we know by how much?

If they have more food, that’s the opposite of CR but then mTOR inhibition might compensate.

Eat more proteins, take Rapamycin!

2 Likes
#327

I asked for a quotation about the cost for repeating the exepriments with killed food.

5 Likes
#328

Just remember that worms are not the best model to use for mammal longevity. What works for worms may not work for mammals and vice versa. It provides a good starting point for mammal trials though. I think if you tried doxycycline in the ITP, you wouldn’t get the same results.

2 Likes
#329

I got the quotation from Ora Medical. To repeat the previous successful experiments, but now with killed food, which costs extra $50 to do, so 250 + 250 = $500
Doxycycline HCl 50 µM + GSK2126458 10 µM
Lithium citrate 25 µM + GSK2126458 25 µM

And at the same time test the following substances also using killed food: Doxycycline HCl 50 µM, GSK2126458 10 µM, Lithium citrate 25 µM and Azithromycin also at a dose of 25 µM. This will be $600 .

Including tax etc., the total sum will be $1,583.72. At this stage this means I will not go through with these experiments will killed food. But If there are others who will join me in a crowdfunding effort, then I will pay $400.

anyone here that is interested?

2 Likes
#330

Ive been sponsoring through vida útil.io with no tax and even a small tax deduction for me. Im happy to help anyone who has to pay a tax. I do want to sponsor gsk with killed food. Is @adssx doing any killed food testing yet?

1 Like
#331

What’s the point of killed food? (I didn’t follow the whole conversation)

#332

C. elegans research methodology, confunding factors killed food vs live food (bacteria):

  1. Living bacteria can metabolize experimental compounds, potentially altering their chemical structure or concentration before the worms consume them.
  2. Bacteria might absorb or sequester certain substances, affecting their bioavailability to the worms.
  3. The lifespan of the bacteria themselves could be affected by experimental conditions, indirectly influencing worm physiology or behavior.
  4. Dead bacteria may have different nutritional profiles or digestibility compared to live bacteria
  5. Lack of metabolic activity: Dead bacteria can’t produce metabolites that might benefit worms
  6. Bacterial colonization, live bacteria can colonize the worm gut, potentially causing infections
  7. Live bacteria may compete with worms for certain nutrients or oxygen.

C. elegans studies, particularly those investigating longevity, drug effects, or specific metabolic pathways, often use killed bacterial lawns (typically UV-irradiated or heat-killed E. coli) to eliminate these variables. The bacterial food source can be especially important in longevity research, as some compounds that initially appeare to extend C. elegans lifespan later might be found to actually be antimicrobials that affects bacterial metabolism rather than directly impacting worm physiology.

#333

I think the better simpler answer is that dead food alone provides significant longevity benefits for c elegans, so antibacteria side effects make compounds look better than they are since it wont transfer to mice or humans.
Read what ora said Ora Biomedical Million Molecule Challenge Results - #308 by Josh

2 Likes
#334

@adssx And this message from ora Ora Biomedical Million Molecule Challenge Results - #304 by Josh
Theres some CR confounding effects as well, but apparently theres still debate in science best way to test.

#335

I think all the experiments should be using killed bacteria as default, as live bacteria shorten lifespan independent of aging.

The longer lived the control lifespan the more certain you can be that a geroscience intervention actually affects aging.

In fact, environmental conditions for every model organism should be experimented with until the optimal light, water, food, humidity, movement e.t.c conditions are found. Then this should be used for all experiments going forward.

It’s quite infuriating really, all the wasted time/resources rediscovering “geroscience” interventions like Metformin which we already know extend life/healthspan if you have insulin resistance, otherwise why is it prescribed to millions around the world? And you’re going to do another animal study to find the same result?

Please good people, it’s an easy fix. So let’s fix this!

1 Like
#336

Can anyone sponsor heavy water (deuterium) and also CBD?

2 Likes
#337

I think the purpose is just to have a stable platform and to look for a molecule which has effects on fundamental drivers of aging. Obviously a lot of drugs which work in humans (or rodents) won’t work in worms. But something which ‘globally’ slows the entire process of aging should still show up. Plus, it’s very easy to repeat things which this setup.

I agree with you that it’s frustrating, and the best results are essentially artifacts of the experimental setup. But hopefully some cool stuff is discovered in the future.

1 Like
#338

Thanks. I can pay $400 as well.

1 Like
#339

How much are you at now? Do you have what is needed?

#340

So far I am at 800 $, one more person is interested but have not given a specific amount of $.

#341

@Curious Ok, I can add $200

Can you ask the person you mentioned how much they can do and then perhaps when others see that we are close they can chip in a bit

#342

I can contribute 100 dollars

#343

So far:
Curious - $400
@adssx - $400
@Neo - $200
@LGalindo - $100
@Josh are you interested?

2 Likes